Inhibitor of growth (ING) domain of inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. ING2 contains an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  23 LECVESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKAERDGAQRKRLQVQLQRALIVSQELGDEKIHVVTQMTELV 102
Cdd:cd16861     1 LECVESLPLEIQRNVSLLREIDTKYQEALKEVDEVYEKYKKETDPSQKKRLQQQLQRALINSQELGDEKIQIVTQMLELV 80

                  ....*...
gi 1929391719 103 ENRSRQME 110
Cdd:cd16861    81 ENRARQME 88

Inhibitor of growth (ING) domain of inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. ING2 contains an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  23 LECVESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKAERDGAQRKRLQVQLQRALIVSQELGDEKIHVVTQMTELV 102
Cdd:cd16861     1 LECVESLPLEIQRNVSLLREIDTKYQEALKEVDEVYEKYKKETDPSQKKRLQQQLQRALINSQELGDEKIQIVTQMLELV 80

                  ....*...
gi 1929391719 103 ENRSRQME 110
Cdd:cd16861    81 ENRARQME 88

Inhibitor of growth proteins N-terminal histone-binding; Histones undergo numerous post-translational modifications, including acetylation and methylation, at residues which are then probable docking sites for various chromatin remodelling complexes. Inhibitor of growth proteins (INGs) specifically bind to residues that have been thus modified. INGs carry a well-characterized C-terminal PHD-type zinc-finger domain, binding with lysine 4-tri-methylated histone H3 (H3K4me3), as well as this N-terminal domain that binds unmodified H3 tails. Although these two regions can bind histones independently, together they increase the apparent association of the ING for the H3 tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  18 YVEDYLECVESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKA---ERDGAQRKRLQVQLQRALIVSQELGDEKIHV 94
Cdd:pfam12998   1 YLEDYLDDLENLPLELQRNFTELREIDAKVQELLKEIDSQIQKFIKqngSLTPNPKEEELSKIQEELKKAQELQDEKIQL 80

                          90
                  ....*....|....*...
gi 1929391719  95 VTQMTELVENRSRQMESH 112
Cdd:pfam12998  81 ANQALELVDKHIRRLDLD 98

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1929391719  238 GEMIGCDneQCPiEWFHFSCVGLTYK---PKGKWYCPKC 273
Cdd:smart00249  12 GELLQCD--GCD-RWYHQTCLGPPLLeeePDGKWYCPKC 47

Inhibitor of growth (ING) domain of inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. ING2 contains an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  23 LECVESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKAERDGAQRKRLQVQLQRALIVSQELGDEKIHVVTQMTELV 102
Cdd:cd16861     1 LECVESLPLEIQRNVSLLREIDTKYQEALKEVDEVYEKYKKETDPSQKKRLQQQLQRALINSQELGDEKIQIVTQMLELV 80

                  ....*...
gi 1929391719 103 ENRSRQME 110
Cdd:cd16861    81 ENRARQME 88

PHD finger found in inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. ING2 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1929391719 228 TYCLCEQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKCRGD 276
Cdd:cd15683     1 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKCRGD 49

Inhibitor of growth (ING) domain of inhibitor of growth protein ING1, ING2, and similar proteins; ING1 is an epigenetic regulator and a type II tumor suppressor that impacts cell growth, aging, apoptosis, and DNA repair, by affecting chromatin conformation and gene expression. It acts as a reader of the active chromatin mark, the trimethylation of histone H3 lysine 4 (H3K4me3). It binds and directs growth arrest and DNA damage inducible protein 45 a (Gadd45a) to target sites, thus linking the histone code with DNA demethylation. It interacts with the proliferating cell nuclear antigen (PCNA) via the PCNA-interacting protein (PIP) domain in a UV-inducible manner. It also interacts with a PCNA-interacting protein, p15 (PAF). Moreover, ING1 associates with members of the 14-3-3 family, which is necessary for cytoplasmic relocalization. Endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX and colocalizes with BAX in a UV-inducible manner. It stabilizes the p53 tumor suppressor by inhibiting polyubiquitination of multi-monoubiquitinated forms via interaction with and colocalization of the herpesvirus-associated ubiquitin-specific protease (HAUSP)-deubiquitinase with p53. It is also involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells. In addition, tyrosine kinase Src can bind and phosphorylate ING1 and further regulates its activity. ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. Both ING1 and ING2 contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  23 LECVESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKY-KAERDGAQRKRLQVQLQRALIVSQELGDEKIHVVTQMTEL 101
Cdd:cd16857     1 LDCVENLPGDVQRNLSLMRELDKRYQEILNELEELYEEYlREDDESHAKKRLLARIQKLLIRSQELGDEKLQIVSQILDL 80

                  ....*....
gi 1929391719 102 VENRSRQME 110
Cdd:cd16857    81 IENRNRQLE 89

PHD finger found in inhibitor of growth protein 1 (ING1); ING1 is an epigenetic regulator and a type II tumor suppressor that impacts cell growth, aging, apoptosis, and DNA repair, by affecting chromatin conformation and gene expression. It acts as a reader of the active chromatin mark, the trimethylation of histone H3 lysine 4 (H3K4me3). It binds and directs Growth arrest and DNA damage inducible protein 45 a (Gadd45a) to target sites, thus linking the histone code with DNA demethylation. It interacts with the proliferating cell nuclear antigen (PCNA) via the PCNA-interacting protein (PIP) domain in a UV-inducible manner. It also interacts with a PCNA-interacting protein, p15 (PAF). Moreover, ING1 associates with members of the 14-3-3 family, which is necessary for the cytoplasmic relocalization. Endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX and colocalizes with BAX in a UV-inducible manner. It stabilizes the p53 tumor suppressor by inhibiting polyubiquitination of multi-monoubiquitinated forms via interaction with and colocalization of the herpesvirus-associated ubiquitin-specific protease (HAUSP)-deubiquitinase with p53. It is also involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells. In addition, tyrosine kinase Src can bind phosphorylate ING1 and further regulates its activity. ING1 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1929391719 228 TYCLCEQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKCRGD 276
Cdd:cd15682     1 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 49

PHD finger found in the inhibitor of growth (ING) protein family; The ING family includes a group of tumor suppressors, ING1-5, which act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1929391719 229 YCLCEQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKC 273
Cdd:cd15505     1 YCICNQVSYGEMVACDNPNCPIEWFHFECVGLTAKPKGKWYCPEC 45

PHD finger found in inhibitor of growth protein 3 (ING3) and similar proteins; ING3, also termed p47ING3, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It is ubiquitously expressed and has been implicated in transcription modulation, cell cycle control, and the induction of apoptosis. It is an important subunit of human NuA4 histone acetyltransferase complex, which regulates the acetylation of histones H2A and H4. Moreover, ING3 promotes ultraviolet (UV)-induced apoptosis through the Fas/caspase-8-dependent pathway in melanoma cells. It physically interacts with subunits of E3 ligase Skp1-Cullin-F-boxprotein complex (SCF complex) and is degraded by the SCF (F-box protein S-phase kinase-associated protein 2, Skp2)-mediated ubiquitin-proteasome system. It also acts as a suppression factor during tumorigenesis and progression of hepatocellular carcinoma (HCC). ING3 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1929391719 229 YCLCEQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKC 273
Cdd:cd15585     1 YCICNQVSYGEMVGCDNDDCPIEWFHYGCVGLTEAPKGKWYCPQC 45

PHD finger found in yeast orthologs of ING tumor suppressor family; The yeast orthologs of the plant homeodomain (PHD) finger-containing ING tumor suppressor family consists of chromatin modification-related protein YNG1 (Yng1p), YNG2 (Yng2p), and transcriptional regulatory protein PHO23 (Pho23p). Yng1p, also termed ING1 homolog 1, is one of the components of the NuA3 histone acetyltransferase (HAT) complex. Its PHD finger binding to H3 Trimethylated at K4 (H3K4me3) promotes NuA3 H3 HAT activity at K14 of H3 on chromatin. Yng2p, also termed ESA1-associated factor 4, or ING1 homolog 2, is a subunit of the NuA4 HAT complex. It plays a critical role in intra-S-phase DNA damage response. Pho23p is part of the Rpd3/Sin3 histone deacetylase (HDAC) complex. It is required for the normal function of Rpd3 in the silencing of rDNA, telomeric, and mating-type loci. Yng1p and Pho23p inhibit p53-dependent transcription. In contrast, Yng2p has the opposite effect. All family members contain an N-terminal ING histone-binding domain and a C-terminal PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1929391719 229 YCLCEQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKC 273
Cdd:cd15587     1 YCYCRRVSFGEMVACDNPDCKIEWFHFECVGLTETPKGKWYCSDC 45

Inhibitor of growth (ING) domain family; The Inhibitor of growth (ING) family includes a group of tumor suppressors, ING1-5, which act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation, and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain that binds unmodified H3 tails, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain, which binds lysine 4-tri-methylated histone H3 (H3K4me3). Although these two regions can bind histones independently, together they increase the apparent association of the ING domain for the H3 tail. The ING family also includes three yeast orthologs, chromatin modification-related protein YNG1 (Yng1p), YNG2 (Yng2p), and transcriptional regulatory protein PHO23 (Pho23p). Yng1p, also termed ING1 homolog 1, is one of the components of the NuA3 histone acetyltransferase (HAT) complex. Yng2p, also termed ESA1-associated factor 4, or ING1 homolog 2, is a subunit of the NuA4 HAT complex. It plays a critical role in intra-S-phase DNA damage response. Pho23p is part of Rpd3/Sin3 histone deacetylase (HDAC) complex. It is required for the normal function of Rpd3 in the silencing of rDNA, telomeric, and mating-type loci. Yng1p and Pho23p inhibit p53-dependent transcription. In contrast, Yng2p has the opposite effect.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  26 VESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKAE---RDGAQRKRLQVQLQRALIVSQELGDEKIHVVTQMTELV 102
Cdd:cd16101     1 LSHLPFELRRLLTLIRELDEKKTELQKEIDELAKELLKSariESHQQKRRLLDEIRQLYEKSIELSDEKVQLSSQAYELV 80

                  ....*...
gi 1929391719 103 ENRSRQME 110
Cdd:cd16101    81 DNHIRKLD 88

Inhibitor of growth (ING) domain of inhibitor of growth protein 4 (ING4); ING4, also termed p29ING4, is a member of the inhibitor of growth (ING) family of type II tumor suppressors. It acts as an E3 ubiquitin ligase to induce ubiquitination of the p65 subunit of NF-kappaB and inhibit the transactivation of NF-kappaB target genes. It also induces apoptosis through a p53 dependent pathway, including increasing p53 acetylation, inhibiting Mdm2-mediated degradation of p53 and enhancing the expression of p53 responsive genes both at the transcriptional and post-translational levels. Moreover, ING4 can inhibit the translation of proto-oncogene MYC by interacting with AUF1. It also regulates other transcription factors, such as hypoxia-inducible factor (HIF). In addition, ING4 associates with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further directs the MOZ/MORF and HBO1 complexes to chromatin. ING4 contains an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  23 LECVESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKAER---DGAQRKRLQVQLQRALIVSQELGDEKIHVVTQMT 99
Cdd:cd16862     1 LDSIENLPFELQRNFQLMRDLDQRTEDLKVEIDKLATEYVSNArslSSEEKLKLLKQIQEAYGKCKEFGDDKVQLAMQTY 80

                          90
                  ....*....|..
gi 1929391719 100 ELVENRSRQMES 111
Cdd:cd16862    81 EMVDKHIRRLDT 92

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1929391719  238 GEMIGCDneQCPiEWFHFSCVGLTYK---PKGKWYCPKC 273
Cdd:smart00249  12 GELLQCD--GCD-RWYHQTCLGPPLLeeePDGKWYCPKC 47

PHD finger found in CXXC-type zinc finger protein 1 (Cfp1); Cfp1, also termed CpG-binding protein, or PHD finger and CXXC domain-containing protein 1 (PCCX1), is a specificity factor that binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). It integrates both promoter CpG content and gene activity for accurate trimethylation of histone H3 Lys 4 (H3K4me3) deposition in embryonic stem cells. Moreover, Cfp1 is an essential component of the SETD1 histone H3K4 methyltransferase complex and functions as a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Cfp1 contains a plant homeodomain (PHD) finger, a CXXC domain, and a CpG binding protein zinc finger C-terminal domain. Its CXXC domain selectively binds to non-methylated CpG islands, following by a preference for a guanosine nucleotide.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1929391719 229 YCLCEQVSYGE-MIGCDNeqCPiEWFHFSCVGLTYK-PKG--KWYCPKC 273
Cdd:cd15553     1 YCICRSSDISRfMIGCDN--CE-EWYHGDCINITEKeAKAikEWYCQQC 46

PHD finger found in Saccharomyces cerevisiae extracellular matrix protein 5 (Ecm5p), Schizosaccharomyces pombe Lid2 complex component Lid2p, and similar proteins; The family includes Saccharomyces cerevisiae Ecm5p, Schizosaccharomyces pombe Lid2 complex component Lid2p, and similar proteins. Ecm5p is a JmjC domain-containing protein that directly removes histone lysine methylation via a hydroxylation reaction. It associates with the yeast Snt2p and Rpd3 deacetylase, which may play a role in regulating transcription in response to oxidative stress. Ecm5p promotes oxidative stress tolerance, while Snt2p ultimately decreases tolerance. Ecm5p contains an N-terminal ARID domain, a JmjC domain, and a C-terminal plant homeodomain (PHD) finger. Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model includes the second PHD finger of Lid2p.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1929391719 229 YCLCEQVSYGEMIGCdnEQCPiEWFHFSCVG---LTYKPKGKWYCPKC 273
Cdd:cd15518     1 YCFCRQGEGGTMIEC--EICK-EWYHVKCIKngrWKLDDDDKFVCPIC 45

Inhibitor of growth (ING) domain of inhibitor of growth protein 5 (ING5); ING5, also termed p28ING5, is a member of the inhibitor of growth (ING) family of type II tumor suppressors. It acts as a Tip60 cofactor that acetylates p53 at K120 and subsequently activates the expression of p53-dependent apoptotic genes in response to DNA damage. Aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and colorectal cancer. ING5 can physically interact with p300 and p53 in vivo, and its overexpression induces apoptosis in colorectal cancer cells. It also associates with Inhibitor of cyclin A1 (INCA1) and functions as a growth suppressor with suppressed expression in Acute Myeloid Leukemia (AML). Moreover, ING5 translocation from the nucleus to the cytoplasm might be a critical event for carcinogenesis and tumor progression in human head and neck squamous cell carcinoma. In addition, ING5 associates with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further directs the MOZ/MORF and HBO1 complexes to chromatin. ING5 contains an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  26 VESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKYKAE-RDGAQRKRLQV--QLQRALIVSQELGDEKIHVVTQMTELV 102
Cdd:cd16863     3 IENLPCELQRNFQLMRDLDQRTEDKKAEIDKLASEYIANvKNLSPEQRVEHlkKIQSAYSKCKEYSDDKVQLAMQTYEMV 82

                  ....*....
gi 1929391719 103 ENRSRQMES 111
Cdd:cd16863    83 DKHIRRLDA 91

PHD finger 5 found in nuclear SET domain-containing protein 3 (NSD3); NSD3, also termed histone-lysine N-methyltransferase NSD3, or protein whistle, or WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fifth PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1929391719 238 GEMIGCDNEQCPiEWFHFSCVGLTYKPKGKWYCP 271
Cdd:cd15661     9 GELVMCDKKDCP-KAYHLLCLNLTQPPYGKWECP 41

PHD finger found in Set1 complex component SPP1; Set1C component SPP1, also called COMPASS component Spp1, or Complex proteins associated with set1 protein Spp1, or Suppressor of PRP protein 1, is a component of the COMPASS complex that links histone methylation to initiation of meiotic recombination. It induces double-strand break (DSB) formation by tethering to recombinationally cold regions. SPP1 interacts with H3K4me3 and Mer2, a protein required for DSB formation, to promote recruitment of potential meiotic DSB sites to the chromosomal axis. SPP1 contains a PHD finger, a zinc binding motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1929391719 229 YCLCEQVSYGE-MIGCDneQCPiEWFHFSCVGLTYKPKG---KWYCPKC 273
Cdd:cd16039     1 YCICQKPDDGRwMIACD--GCD-EWYHFTCVNIPEADVElvdSFFCPPC 46

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

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gi 1929391719 230 CLCEQVSY--GEMIGCDneQCPIeWFHFSCVGLTYK---PKGKWYCPKC 273
Cdd:cd15489     3 IVCGKGGDlgGELLQCD--GCGK-WFHADCLGPPLSsfvPNGKWICPVC 48

PHD finger 5 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or Lysine N-methyltransferase 3B (KMT3B), or NR-binding SET domain-containing protein, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription. It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma and glioblastoma formation. It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fifth PHD finger.

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gi 1929391719 238 GEMIGCDNEQCPiEWFHFSCVGLTYKPKGKWYCP 271
Cdd:cd15659     9 GQLVSCKKPGCP-KVYHADCLNLTKRPAGKWECP 41

Inhibitor of growth (ING) domain of inhibitor of growth protein 3 (ING3), Yng2p and similar proteins; ING3, also termed p47ING3, is a member of the inhibitor of growth (ING) family of type II tumor suppressors. It is ubiquitously expressed and has been implicated in transcription modulation, cell cycle control, and the induction of apoptosis. It is an important subunit of human NuA4 histone acetyltransferase complex, which regulates the acetylation of histones H2A and H4. Moreover, ING3 promotes ultraviolet (UV)-induced apoptosis through the Fas/caspase-8-dependent pathway in melanoma cells. It physically interacts with subunits of E3 ligase Skp1-Cullin-F-boxprotein complex (SCF complex) and is degraded by the SCF (F-box protein S-phase kinase-associated protein 2, Skp2)-mediated ubiquitin-proteasome system. It also acts as a suppression factor during tumorigenesis and progression of hepatocellular carcinoma (HCC). Yeast chromatin modification-related protein Yng2p, also termed ESA1-associated factor 4 or ING1 homolog 2, is a subunit of the NuA4 histone acetyltransferase (HAT) complex. It plays a critical role in intra-S-phase DNA damage response. Members of this family contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1929391719  26 VESLPLDIQRNVSVLREIDAKYQEVLKEVDEVFEKY-------KAERDGAQRKRLQVQLQRALIVSQELGDEKIHVVTQM 98
Cdd:cd16858     1 LENLPSELRHLLTEIREKDLQVQELLDRIQQRDAKLfkhikknGSLTPNPKEEELYEKIREDYDKALELADEKVELANRL 80

                  ....*
gi 1929391719  99 TELVE 103
Cdd:cd16858    81 LDLVD 85

PHD finger 1 found in nuclear receptor-binding SET domain-containing protein NSD1 and NSD2; NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or Lysine N-methyltransferase 3B (KMT3B), or NR-binding SET domain-containing protein, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription. It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD2, also termed histone-lysine N-methyltransferase NSD2, or multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). Both NSD1 and NSD2 contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). In addition, NSD2 harbors a high mobility group (HMG) box. The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks. This model corresponds to the first PHD finger.

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gi 1929391719 231 LCEQVsyGEMIGCDNEQCPIewFHFSCVGLTYKPKGKWYCPKCR 274
Cdd:cd15648     4 VCEKP--GELLLCEGQCCGA--FHLDCIGLSEMPSGKFICDECI 43

PHD finger found in PHF2, PHF8 and KDM7; This family includes PHF2, PHF8, KDM7, and similar proteins. PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. PHF8, also termed PHD finger protein 8, or KDM7B, is a monomethylated histone H4 lysine 20(H4K20me1) demethylase that transcriptionally regulates many cell cycle genes. It also preferentially acts on H3K9me2 and H3K9me1. PHF8 is modulated by CDC20-containing anaphase-promoting complex (APC (cdc20)) and plays an important role in the G2/M transition. It acts as a critical molecular sensor for mediating retinoic acid (RA) treatment response in RAR alpha-fusion-induced leukemia. Moreover, PHF8 is essential for cytoskeleton dynamics and is associated with X-linked mental retardation. KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. All family members contain a plant homeodomain (PHD) finger and a JmjC domain.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1929391719 229 YCLCEQVsYGE---MIGCDneQCPiEWFHFSCVGL---TYKPKGKWYCPKC 273
Cdd:cd15554     1 YCICRQP-YDVtrfMIECD--VCK-DWFHGSCVGVeehQANDIERYHCPNC 47

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interaction with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

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gi 1929391719 241 IGCDneQCPiEWFHFSCVGLT---YKPKGKWYCPKC 273
Cdd:cd15517    17 VQCD--GCD-KWFHQFCLGLSnerYADEDKFKCPNC 49

PHD finger 2 found in PHD finger protein 10 (PHF10) and similar proteins; PHF10, also termed BRG1-associated factor 45a (BAF45a), or XAP135, is a ubiquitously expressed transcriptional regulator that is required for maintaining the undifferentiated status of neuroblasts. It contains a SAY (supporter of activation of yellow) domain and two adjacent plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

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gi 1929391719 238 GEMIGCDneQCPiEWFHFSCVGLTYKPKGKWYCPKC 273
Cdd:cd15529    12 DKMMFCD--QCD-RGYHTFCVGLRSIPDGRWICPLC 44